EFFECTS OF 5-HT3 RECEPTOR ANTAGONISM ON HIPPOCAMPAL CELLULAR ACTIVITY IN
THE FREELY MOVING RAT.
Reznic, Jeffrey and Ursula Staubli.
Center for Neural Science, New York University, New York, NY 10003 .APStracts 3:0230N, 1996.
ABSTRACT
Recent physiological studies conducted in the hippocampus of freely moving
rats have revealed that systemic injections of the selective 5-HT 3 receptor
antagonist ondansetron facilitate LTP induction, increase the frequency of the
theta EEG rhythm, and enhance retention of memory in hippocampally-dependent
tasks. To gain insight into the cellular mechanisms underlying these
observations, the present study examined the effects of intraperitoneal (i.p.)
injections of ondansetron on the firing rate of CA1 interneurons and pyramidal
cells in the dorsal hippocampus of freely moving rats. Mean firing rates of a
substantial proportion (17/27) of isolated neurons were significantly
different between pre- and post-ondansetron injection (500 and 1000 [mu]
g/kg). Of the interneurons that exhibited an effect, all (11/11) significantly
decreased their mean firing rate, with an average change of -22.4 + 3.9 %
(mean + S.E.M.) across cells. Eighty-three percent (5/6) of pyramidal cells
showing a change in mean firing rate displayed a significant increase in
activity, with an average change of 56.3 + 25.6 % (mean + S.E.M.) across
cells. Ondansetron (1.0 mg/kg, i.p.) had no detectable effect on spontaneous
behavioral activity as measured by line-crossings and rearings in an open-
field apparatus. The present results show that pharmacological blockade of 5-
HT 3 receptors causes a reduction in firing activity of a subset of CA1
hippocampal interneurons, with concomitant increases in the firing rate of
pyramidal cells. These changes may be directly related to the ondansetron-
induced enhancement of LTP induction and memory formation observed in previous
studies.

Received 1996; accepted in final form 1996.
APS Manuscript Number J.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996